A new study, presented at the SNM 55th Annual Meeting, shows the potential to pre-target the treatment of cancer cells--bringing personalized medicine one step closer from the laboratory to patients. By combining new molecular imaging techniques with targeted therapy, pretargeting offers cancer patients a more individualized treatment that can increase the effectiveness of therapies and minimize discomfort experienced during treatment.
In traditional radioimmunoimaging (RAII), radioisotopes are linked directly to antibodies and are delivered together to tumor targets. However, antibodies are relatively large molecules designed to remain in the bloodstream for a long period of time to fight infections, and their slow blood clearance can present difficulties when they are used to carry radioactive materials. The excessive blood-pool activity masks the radioisotope uptake in tumor lesions, thereby lowering the sensitivity and limiting the selectivity of traditional RAII.
"This study demonstrates the advantages of pretargeting--an alternative strategy that uses a 'two-step' approach to the delivery of radioisotopes--when applied to the imaging of tumors using a combination of radioisotope and antibody or RAII," said Otto Boerman, professor in the department of nuclear medicine, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands, and lead researcher of this study.
According to Boerman, in this process a bispecific monoclonal antibody (bsMAb), with one arm that recognizes a tumor-associated antigen and another arm that recognizes a peptide carrying an imaging agent, is given as a first injection. When the non-tumor-bound bsMAb has substantially cleared non-target tissues and has reached a maximum level in the tumor, the bsMAb-recognizable imaging agent is given. The latter agent either targets the bsMAb localized at the tumor or is rapidly removed in the urine. Because the delivery of imaging isotopes is rapid and is separated from the long antibody delivery process, radioisotope uptake in the tumor is significantly higher than in the blood, making pretargeting RAII an attractive alternative to traditional RAII.
"Pretargeting has applications beyond molecular imaging," said Boerman. "As has been demonstrated in this study, pretargeting with bsMAb can also be employed to improve the selective delivery of therapeutic isotopes, as well as cytotoxic drugs, to cancers. In fact, the major attribute of pretargeting is that the same bsMAb can be used for diagnostic imaging and therapy."
In this study, high specific uptake was obtained in human colon cancer cells transplanted in mice, resulting in very high tumor-to-blood and tumor-to-kidney ratios of radioisotope uptake. Additionally, PET/CT imaging of mice pretargeted with the bispecific antibody 16 hours earlier revealed excellent high-contrast images of CEA-expressing tumors within one hour after injection of the radionuclide gallium-68 (Ga-68)-labeled histamine-succinyl-glycine (HSG) peptide.
"When the imaging component of a pretargeting agent is used in concert with the therapeutic component, it permits the selection of a patient population that over-expresses a particular antigen, thus increasing these pre-screened patients' probability of responding to the therapeutic" said Boerman. "The prescreening of patients afforded by pretargeting prior to therapy represents a potential major advancement in the management of neoplastic diseases.
Reference: Scientific Paper 209: O.C. Boerman, G. Franssen, R. Schoffellen, W. van der Graff, W.J. Oyen, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; R.M. Sharkey, D.M. Goldenberg, Garden State Cancer Center, Belleville, N.J.; C. Chang, E.A. Rossi, W.J. McBride, Immunomedics, Morris Plains, N.J., "Pretargeted ImmunoPET Imaging of CEA-Expressing Tumors Using a Ga-68 Labeled Peptide," SNM's 55th Annual Meeting, June 14-18, 2008.
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